Objectives and specific aims are: 1) To develop and characterize a recently developed rat model of thrombotic thrombocytopenic purpura (TTP) induced by a snake venom, botrocetin. The program includes ascertainment of the pathology and pathophysiology of the condition and comparison with the human disease. Alterations in hemostasis, plasma factor VIII complex, platelet function and endothelium, will be determined. Evolution and resolution of microvascular thrombi will be examined. Searches will be made for chemical agents that may prevent or alter the course of the syndrome. Possible mechanisms by which venom coagglutinin induces the disorder will be investigated; (2) To maintain inbred colonies of bleeder animals (von Willebrand disease dogs; hemophilia A and B dogs) as animal models on the corresponding human diseases; to study the genetics and pathophysiology of these diseases in animals and extend the studies, as appropriate to the human counterpart; to determine the comparative effectiveness of different plasma procoagulant fractions, particularly those of the factor VIII complex, both plasma-derived and recombinant as available, in correcting the several defects in these inherited bleeding disorders, as modified by varying gene dosages of the vWD and hemophilia A genes.